A new procedure for the Julia-Colonna stereoselective epoxidation reaction under non-aqueous conditions: The development of a catalyst comprising polyamino acid on silica (PaaSiCat)

Article abstract of DOI:10.1039/a903219c

Polyleucine adsorbed onto silica provides a robust, readily-recycled, highly active catalyst for the asymmetric epoxidation of the α,β-unsaturated ketones 1, 2, and 3.

Full text of DOI:10.1039/a903219c

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A new procedure for the Juliá–Colonna stereoselective epoxidation
reaction under non-aqueous conditions: the development of a
catalyst comprising polyamino acid on silica (PaaSiCat)
Thomas Geller and Stanley M. Roberts
Department of Chemistry, University of Liverpool, Liverpool, UK L69 7ZD
Received (in Cambridge) 22nd April 1999, Accepted 23rd April 1999
Polyleucine adsorbed onto silica provides a robust, readily-
recycled, highly active catalyst for the asymmetric epoxid-
i
pLL + flash silica 60
[pLL/silica]
ation of the á,â-unsaturated ketones 1, 2, and 3.
O
O
The asymmetric epoxidation of α,β-unsaturated ketones using
peroxide anion in the presence of a polyamino acid (paa) such
ii
R
R
as poly--alanine or poly--leucine was discovered by Juliá and
Colonna. In this original procedure the substrate in a water-
immiscible organic solvent, for example toluene, was treated
O
1
1
R=Ph
4
2
3
R=o-aminophenyl
5
6
with aqueous sodium hydroxide containing hydrogen peroxide
and the paa. The insoluble paa was present as a gel-like third
R=CH(CH3)2
2
phase. Though this procedure was used by several workers,
Scheme 1 Catalyst preparation and standard test reaction. Reagents
and conditions: i, THF, 48 h; ii, pLL/silica, UHP, DBU, THF.
several problems were presented by this protocol, not least the
harsh reaction conditions employed, the limited range of
(
chalcone-like) substrates that could be oxidized, the lengthy
reaction times that were needed and, most importantly, the
difficulty in recovery of the gel-like catalyst.
phase-separation is rapid and filtration, as part of the work-up
procedure, is much easier to achieve. The Juliá–Colonna epoxid-
ation employing the polyamino acid-on-silica catalyst (Paa-
SiCat) could be accomplished in a wide range of solvents. In
terms of rate of the reaction (complete conversion in less than
50 min) and enantiomeric excess (≥93% ee) tetrahydrofuran,
pyridine and tert-butyl methyl ether were found to be excellent
solvents.
A more recently developed procedure overcame some of
3
these problems. The new protocol employed a two-phase
system, comprising substrate and a peroxide donor (e.g. urea–
hydrogen peroxide complex) in an organic solvent containing a
base such as diazabicycloundecene (DBU) in the presence of
the insoluble paa. The catalyst was present as a thick paste coat-
ing the inside of the reaction flask. Several advantages of the
two-phase system were immediately apparent. First the reaction
times were decreased by one to two orders of magnitude;
secondly the substrate range was broadened since the use of
aqueous base had been eliminated. Thirdly, recovery of
product was straightforward, involving simple decantation of
solvent and product from the paste-like catalyst.
One problem remained, that is the recovery of catalyst5.
Although it was established that the catalyst could be recycled,
losses of catalyst amounted to ca. 10% per run. Moreover, after
Remarkably the standard test reaction can be carried out
using the PaaSiCat with only 23% of the pLL normally
employed, without any significant influence on the rate of the
11
reaction and enantiomeric excess of the resultant material. In
addition to these advantages the catalyst is extremely robust. In
4
12
contrast to unmodified pLL, it can be heated at 150 ЊC for 12
h under vacuum and retain full catalytic activity! The recyclabil-
ity of the new catalyst was investigated for the standard test
6
reaction. In contrast to our reported results with pLL, no
increase in the reaction time for the epoxidation was observed,
even after six runs with the recycled silica-supported catalyst.
The substantial loss of catalyst observed under normal biphasic
conditions was eliminated. The average mechanical loss per run
of the new material (which contains only 23% of pLL, it should
be emphasized) is about 3%. Recycled material exhibits equally
high catalytic activity when compared to freshly-prepared
catalyst, the enantiomeric excess of epoxide remaining at a
remarkably high level (≥93% ee). The new procedure was tested
with other substrates, namely 1-(2-aminophenyl)-3-phenylprop-
2-en-1-one (2) and 4-methyl-1-phenyl-pent-1-en-3-one (3)
(Table 1). From Table 1 it is obvious that the employment of the
procedure decreases the reaction time significantly while retain-
ing a very high degree of face-selectivity in the oxidation of the
enone.
6
some time, the catalyst had to be reactivated before re-use.
In this paper we present a solution to this problem, by trans-
locating a strategy successfully employed in the field of
biotransformations.
Within the field of biocatalysis it has been demonstrated that
immobilization of enzymes onto a solid support yields material
which normally exhibits an increased degree of activity in
7
organic solvents. Moreover the recycling of an immobilized
enzyme is much easier. The concept of immobilization of
enzymes was applied to the synthetic polyamino acid poly--
leucine (pLL). In initial adsorption experiments several
materials were tested as solid carriers for pLL. The ratio of
polyamino acid to solid support was chosen to be similar to the
8
9
ratio used by Carrea for the immobilization of lipase PS. The
new materials were compared to the parent (unmodified) pLL
In conclusion we believe that this new protocol is the method
of choice for conducting the Juliá–Colonna epoxidation of
enones. The new catalyst is easy to prepare and has a signifi-
cantly higher activity than the non-adsorbed pLL. Further-
more the work-up procedure is very much easier making
recycling of the catalyst very simple, such that the loss of
catalyst is minimized. In general the yields are higher with
the PaaSiCat than those obtained with unmodified pLL.
This discovery gives access to a robust, simple-to-use, highly
active asymmetric epoxidation catalyst from commercially
10
in the “standard” test reaction, namely Weitz–Scheffer epoxid-
ation of enone 1 to give the epoxide 4 (Scheme 1). From among
these new materials the silica-based catalyst is outstanding.
Besides demonstrating a significantly increased catalytic activ-
ity the physical properties of the new material are (as expected)
totally different from the unmodified pLL. Whereas unmodified
pLL forms a paste during the course of the reaction the new
catalyst retained its granular appearance; also there is no
observable swelling of the catalyst. When the stirring is stopped
J. Chem. Soc., Perkin Trans. 1, 1999, 1397–1398
1397

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Table 1 Epoxidation of enone 2 and 3 using pLL or pLL on silica
a
a
Entry
Enone
Catalyst
t/h
Conversion (%)
Epoxide (ee) (%)
1
2
3
4
2
2
3
3
pLL
PLL/silica
pLL
3
3
26
14
35
85
56
78
5 (n.e.)
5 (93)
6 (89)
6 (93)
PLL/silica
a
Conversion and ee determined by HPLC; n.e. - not evaluated.
available pLL and commonly used “flash” silica, and further
investigations are in progress to define the range of substrates
undergoing reaction. All the details will be described in a
forthcoming full paper, but even at this early stage it is
quite clear that the method compares favourably with other
recently published methods for the asymmetric epoxidation of
2 H. van Rensburg, P. S. Heerden, B. C. B. Bezuidenhoudt and
D. Ferreira, Tetrahedron, 1997, 53, 14141; R. J. J. Niel, P. S. van
Heerden, H. van Rensburg and D. Ferreira, Tetrahedron Lett., 1998,
3
1
9, 5623; J. R. Falck, R. K. Bhatt, K. M. Reddy and J. Ye, Synlett,
997, 481; P. W. Baures, D. S. Eggleston, J. R. Flisak, K. J. Gombatz,
I. Lantos, W. L. Mendelson and J. J. Remich, Tetrahedron Lett.,
990, 31, 6501.
P. A. Bentley, S. Bergeron, M. W. Cappi, D. E. Hibbs, M. B. Hurst-
house, T. C. Nugent, R. Pulido, S. M. Roberts and L. E. Wu, Chem.
Commun., 1997, 739; B. M. Adger, J. V. Barkley, S. Bergeron,
M. W. Cappi, B. E. Flowerdew, M. P. Jackson, R. McCague,
T. C. Nugent and S. M. Roberts, J. Chem. Soc., Perkin Trans. 1,
1
13
α,β-unsaturated ketones.
3
4
Experimental
Preparation of catalyst
1
997, 3501; see also R. M. Savizky, N. Suzuki and J. L. Bové, Tetra-
pLL (1 g) and silica gel 60 (3.4 g, 230–400 mesh, Merck) were
mixed in a 100 ml round bottomed flask and then suspended in
THF (30 ml anhydrous). The flask was sealed with a septum
and the mixture stirred in the dark for 48 h (magnetic stirrer,
slow stirring rate). The suspension was then filtered (glass sinter
porosity 3) and the solid residue washed with 2 × 10 ml of
anhydrous THF. The catalyst was dried under vacuum (1 h, 11
mbar, room temp., then 1 h, 0.08 mbar, 50 ЊC).
hedron: Asymmetry, 1998, 9, 3967.
J. V. Allen, M. W. Cappi, P. D. Kary, S. M. Roberts, N. M.
Williamson and L. E. Wu, J. Chem. Soc., Perkin Trans. 1, 1997,
3
297; for a full discussion on the range of substrates epoxidized
efficiently in the two-phase system see J. V. Allen, S. M. Roberts and
N. M. Williamson, Adv. Biochem. Eng./Biotechnol., 1998, 63, 125.
J. R. Flisak, K. J. Gombatz, M. M. Holmes, A. A. Jarmas, I. Lantos,
W. L. Mendelson, V. J. Novack, J. J. Remich and L. Snyder, J. Org.
Chem., 1993, 58, 6247.
5
6
J. V. Allen, S. Bergeron, M. J. Griffiths, S. Mukherjee, S. M. Roberts,
N. M. Williamson and L. E. Wu, J. Chem. Soc., Perkin Trans. 1,
Typical procedure for an epoxidation reaction
1
998, 3171.
Ϫ5
A mixture of the enone (8.6 × 10 mol), urea–hydrogen per-
7 For example see J. Partridge, P. J. Halling and B. D. Moore, Chem.
Commun., 1998, 841 and references therein.
8 PLL was prepared according to S. Itsuno, M. Sakkura and K. Ito,
J. Org. Chem., 1990, 55, 6047 and adsorbed onto the following
materials: aluminium oxide (activated, neutral, Brockmann 1, STD
grade, 150 mesh); Celite HyfloSuperCel; CPC (375 Å, 30–45
mesh); 3-aminopropyl derivatized CPC (375 Å, 30–45 mesh); silica
oxide adduct (10 mg, 1.2 equiv.) and catalyst (155 mg) were
suspended in THF (1 ml, anhydrous) and DBU (15 µl, 1.2
equiv.) was added. After the completion of the reaction the
mixture was filtered and the solid residue washed with EtOAc
(
(
5 × 2 ml). The organic phase was treated with aqueous Na SO3
20% solution). After phase-separation, the organic phase was
2
gel 60 (230–400 mesh); Wessalith Day P; molecular sieve (SiO );
2
washed with brine, dried (MgSO ) and the solvent evaporated
4
molecular sieve (Na/Al silicate); zeolite TS 1 (5.5 Å, 3% Ti).
R. Bovara, G. Carrea, L. Ferarra and S. Riva, Tetrahedron: Asym-
metry, 1991, 2, 931.
under reduced pressure. Measurements of enantiomeric excess
9
were conducted by HPLC (Chiralpak AD, Daicel): a) epoxide
Ϫ1
4
: 254 nm, EtOH–hexane 1:9, 1.0 mL min , b) epoxide 5: 230
10 B. C. Das and J. Iqbal, Tetrahedron Lett., 1997, 38, 1235.
11 Further reduction in the amount of pLL/silica employed led to a
decreased rate of reaction and a drop in enantioselectivity.
2 P. A. Bentley, W. Kroutil, J. A. Littlechild and S. M. Roberts,
Chirality, 1997, 9, 198.
3 For example M. Bougauchi, S. Watanabe, T. Arai, H. Sasai and
M. Shibasaki, J. Am. Chem. Soc., 1997, 119, 2329; C. L. Elston,
R. F. W. Jackson, S. J. F. MacDonald and P. J. Murray, Angew.
Chem., Int. Ed. Engl., 1997, 36, 410.
Ϫ1
nm, EtOH–hexane 7:43, 1 mL min , c) epoxide 6: 230 nm,
EtOH–hexane 0.5:9.5, 0.7 mL min . EtOH contains 0.7% of
Ϫ1
1
H O.
2
1
References
1
S. Banfi, S. Colonna, H. Molinari, S. Juliá and J. Guixer, Tetra-
hedron, 1984, 40, 5207 and references cited therein; reviewed by
S. Ebrahim and M. Wills, Tetrahedron: Asymmetry, 1997, 7, 3163;
L. Pu, Tetrahedron: Asymmetry, 1998, 9, 1457.
Communication 9/03219C
1
398
J. Chem. Soc., Perkin Trans. 1, 1999, 1397–1398